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Aliases for WNK4 Gene

Aliases for WNK4 Gene

  • WNK Lysine Deficient Protein Kinase 4 2 3 5
  • Protein Kinase Lysine-Deficient 4 3 4
  • Protein Kinase With No Lysine 4 3 4
  • EC 2.7.11.1 4 63
  • PRKWNK4 3 4
  • Protein Kinase, Lysine Deficient 4 2
  • EC 2.7.11 63
  • PHA2B 3

External Ids for WNK4 Gene

Previous HGNC Symbols for WNK4 Gene

  • PRKWNK4

Previous GeneCards Identifiers for WNK4 Gene

  • GC17P038188
  • GC17P040932
  • GC17P036697
  • GC17P042780
  • GC17P042881

Summaries for WNK4 Gene

Entrez Gene Summary for WNK4 Gene

  • This gene encodes a member of the WNK family of serine-threonine protein kinases. The kinase is part of the tight junction complex in kidney cells, and regulates the balance between NaCl reabsorption and K(+) secretion. The kinase regulates the activities of several types of ion channels, cotransporters, and exchangers involved in electrolyte flux in epithelial cells. Mutations in this gene result in pseudohypoaldosteronism type IIB.[provided by RefSeq, Sep 2009]

GeneCards Summary for WNK4 Gene

WNK4 (WNK Lysine Deficient Protein Kinase 4) is a Protein Coding gene. Diseases associated with WNK4 include pseudohypoaldosteronism, type iib and pseudohypoaldosteronism. Among its related pathways are Transport of glucose and other sugars, bile salts and organic acids, metal ions and amine compounds and Cytoskeleton remodeling Regulation of actin cytoskeleton by Rho GTPases. GO annotations related to this gene include transferase activity, transferring phosphorus-containing groups and protein tyrosine kinase activity. An important paralog of this gene is NRBP1.

UniProtKB/Swiss-Prot for WNK4 Gene

  • Serine/threonine kinase which plays an important role in the regulation of electrolyte homeostasis, cell signaling, survival and proliferation. Acts as an activator and inhibitor of sodium-coupled chloride cotransporters and potassium-coupled chloride cotransporters respectively. Activates SCNN1A, SCNN1B, SCNN1D, SGK1, TRPV5 and TRPV6. Regulates the activity of the thiazide-sensitive Na-Cl cotransporter, SLC12A3, by phosphorylation which appears to prevent membrane trafficking of SLC12A3. Also inhibits the renal K(+) channel, KCNJ1, via a kinase-independent mechanism by which it induces clearance of the protein from the cell surface by clathrin-dependent endocytosis. WNK4 appears to act as a molecular switch that can vary the balance between NaCl reabsorption and K(+) secretion to maintain integrated homeostasis. Phosphorylates NEDD4L. Acts as a scaffold to inhibit SLC4A4 as well as CFTR activities and surface expression, recruits STK39 which mediates the inhibition (By similarity).

Gene Wiki entry for WNK4 Gene

No data available for Tocris Summary , PharmGKB "VIP" Summary , fRNAdb sequence ontologies and piRNA Summary for WNK4 Gene

Genomics for WNK4 Gene

Regulatory Elements for WNK4 Gene

Promoters for WNK4 Gene
Ensembl Regulatory Elements (ENSRs) TSS Distance (bp) Size (bp) Binding Sites for Transcription Factors within promoters

ENSRs around WNK4 on UCSC Golden Path with GeneCards custom track

Genomic Location for WNK4 Gene

Chromosome:
17
Start:
42,779,673 bp from pter
End:
42,797,066 bp from pter
Size:
17,394 bases
Orientation:
Plus strand

Genomic View for WNK4 Gene

Genes around WNK4 on UCSC Golden Path with GeneCards custom track

Cytogenetic band:
WNK4 Gene in genomic location: bands according to Ensembl, locations according to GeneLoc (and/or Entrez Gene and/or Ensembl if different)
Genomic Location for WNK4 Gene
GeneLoc Logo Genomic Neighborhood Exon StructureGene Density

RefSeq DNA sequence for WNK4 Gene

Proteins for WNK4 Gene

  • Protein details for WNK4 Gene (UniProtKB/Swiss-Prot)

    Protein Symbol:
    Q96J92-WNK4_HUMAN
    Recommended name:
    Serine/threonine-protein kinase WNK4
    Protein Accession:
    Q96J92
    Secondary Accessions:
    • B0LPI0
    • Q8N8X3
    • Q8N8Z2
    • Q96DT8
    • Q9BYS5

    Protein attributes for WNK4 Gene

    Size:
    1243 amino acids
    Molecular mass:
    134739 Da
    Cofactor:
    Name=Mg(2+); Xref=ChEBI:CHEBI:18420;
    Quaternary structure:
    • Interacts with the C-terminal region of KCNJ1 (By similarity). Interacts with WNK1 and WNK3 (By similarity). Interacts with KLHL3.
    SequenceCaution:
    • Sequence=BAC04669.1; Type=Erroneous initiation; Note=Translation N-terminally extended.; Evidence={ECO:0000305}; Sequence=CAC48387.1; Type=Frameshift; Positions=4; Evidence={ECO:0000305};

    Three dimensional structures from OCA and Proteopedia for WNK4 Gene

    Alternative splice isoforms for WNK4 Gene

    UniProtKB/Swiss-Prot:

neXtProt entry for WNK4 Gene

Proteomics data for WNK4 Gene at MOPED

Post-translational modifications for WNK4 Gene

  • Phosphorylated by WNK1 and WNK3.
  • Ubiquitinated by the BCR(KLHL3) complex, leading to its degradation and increased expression of KCNJ1 at the cell surface. Ubiquitinated by the BCR(KLHL2) complex.
  • Ubiquitination at Lys 157, Lys 175, Lys 186, Lys 226, Lys 241, Lys 328, Lys 387, Lys 393, Lys 450, Lys 454, Lys 1010, Lys 1144, Lys 1157, and Lys 1158
  • Modification sites at PhosphoSitePlus

Other Protein References for WNK4 Gene

Antibody Products

  • Cell Signaling Technology (CST) Antibodies for WNK4 (WNK4)

Domains & Families for WNK4 Gene

Gene Families for WNK4 Gene

Protein Domains for WNK4 Gene

Graphical View of Domain Structure for InterPro Entry

Q96J92

UniProtKB/Swiss-Prot:

WNK4_HUMAN :
  • Contains 1 protein kinase domain.
  • Belongs to the protein kinase superfamily. Ser/Thr protein kinase family. WNK subfamily.
Domain:
  • Contains 1 protein kinase domain.
Family:
  • Belongs to the protein kinase superfamily. Ser/Thr protein kinase family. WNK subfamily.
genes like me logo Genes that share domains with WNK4: view

Function for WNK4 Gene

Molecular function for WNK4 Gene

UniProtKB/Swiss-Prot CatalyticActivity:
ATP + a protein = ADP + a phosphoprotein.
UniProtKB/Swiss-Prot EnzymeRegulation:
Activation requires autophosphorylation of Ser-335. Phosphorylation of Ser-331 also promotes increased activity (By similarity).
UniProtKB/Swiss-Prot Function:
Serine/threonine kinase which plays an important role in the regulation of electrolyte homeostasis, cell signaling, survival and proliferation. Acts as an activator and inhibitor of sodium-coupled chloride cotransporters and potassium-coupled chloride cotransporters respectively. Activates SCNN1A, SCNN1B, SCNN1D, SGK1, TRPV5 and TRPV6. Regulates the activity of the thiazide-sensitive Na-Cl cotransporter, SLC12A3, by phosphorylation which appears to prevent membrane trafficking of SLC12A3. Also inhibits the renal K(+) channel, KCNJ1, via a kinase-independent mechanism by which it induces clearance of the protein from the cell surface by clathrin-dependent endocytosis. WNK4 appears to act as a molecular switch that can vary the balance between NaCl reabsorption and K(+) secretion to maintain integrated homeostasis. Phosphorylates NEDD4L. Acts as a scaffold to inhibit SLC4A4 as well as CFTR activities and surface expression, recruits STK39 which mediates the inhibition (By similarity).

Enzyme Numbers (IUBMB) for WNK4 Gene

Gene Ontology (GO) - Molecular Function for WNK4 Gene

GO ID Qualified GO term Evidence PubMed IDs
GO:0005524 ATP binding IEA,ISS --
genes like me logo Genes that share ontologies with WNK4: view
genes like me logo Genes that share phenotypes with WNK4: view

Human Phenotype Ontology for WNK4 Gene

HPO Id HPO Name Alternative Ids Definition Synonyms

Animal Models for WNK4 Gene

MGI Knock Outs for WNK4:

Animal Model Products

  • Taconic Biosciences Mouse Models for WNK4

miRNA for WNK4 Gene

miRTarBase miRNAs that target WNK4

No data available for Transcription Factor Targets and HOMER Transcription for WNK4 Gene

Localization for WNK4 Gene

Subcellular locations from UniProtKB/Swiss-Prot for WNK4 Gene

Cell junction, tight junction. Note=Present exclusively in intercellular junctions in the distal convoluted tubule and in both the cytoplasm and intercellular junctions in the cortical collecting duct. WNK4 is part of the tight junction complex (By similarity). {ECO:0000250}.

Subcellular locations from

COMPARTMENTS
Jensen Localization Image for WNK4 Gene COMPARTMENTS Subcellular localization image for WNK4 gene
Compartment Confidence
nucleus 2
plasma membrane 2
cytosol 1
extracellular 1
golgi apparatus 1
lysosome 1
peroxisome 1
vacuole 1

No data available for Gene Ontology (GO) - Cellular Components for WNK4 Gene

Pathways & Interactions for WNK4 Gene

genes like me logo Genes that share pathways with WNK4: view

Pathways by source for WNK4 Gene

1 GeneGo (Thomson Reuters) pathway for WNK4 Gene

Gene Ontology (GO) - Biological Process for WNK4 Gene

GO ID Qualified GO term Evidence PubMed IDs
GO:0006468 protein phosphorylation IEA,ISS --
GO:0006811 ion transport IEA,ISS --
GO:0006821 chloride transport IEA --
GO:0032414 positive regulation of ion transmembrane transporter activity IBA --
GO:0050794 regulation of cellular process IEA,ISS --
genes like me logo Genes that share ontologies with WNK4: view

No data available for SIGNOR curated interactions for WNK4 Gene

Drugs & Compounds for WNK4 Gene

(7) Drugs for WNK4 Gene - From: HMDB and Novoseek

Name Status Disease Links Group Role Mechanism of Action Clinical Trials
Adenosine triphosphate Approved Nutra 0
Magnesium Nutra 0

(6) Additional Compounds for WNK4 Gene - From: HMDB and Novoseek

Name Synonyms Role CAS Number PubChem IDs PubMed IDs
ADP
  • Adenosindiphosphorsaeure
  • Adenosine 5'-pyrophosphate
  • Adenosine diphosphate
  • Adenosine pyrophosphate
  • Adenosine-5'-diphosphate
Full agonist, Agonist 58-64-0
Chloride ion
  • Bertholite
  • Chloor
  • Chlor
  • Chlore
  • Chloride
16887-00-6
genes like me logo Genes that share compounds with WNK4: view

Transcripts for WNK4 Gene

Unigene Clusters for WNK4 Gene

WNK lysine deficient protein kinase 4:
Representative Sequences:

Alternative Splicing Database (ASD) splice patterns (SP) for WNK4 Gene

No ASD Table

Relevant External Links for WNK4 Gene

GeneLoc Exon Structure for
WNK4
ECgene alternative splicing isoforms for
WNK4

Expression for WNK4 Gene

mRNA expression in normal human tissues for WNK4 Gene

mRNA expression in embryonic tissues and stem cells from LifeMap Discovery

mRNA differential expression in normal tissues according to GTEx for WNK4 Gene

This gene is overexpressed in Colon - Transverse (x9.4), Kidney - Cortex (x8.9), Esophagus - Mucosa (x6.2), and Prostate (x5.6).

Protein differential expression in normal tissues from HIPED for WNK4 Gene

This gene is overexpressed in Heart (53.9) and Rectum (15.1).

Integrated Proteomics: protein expression in normal tissues and cell lines from ProteomicsDB, PaxDb, MOPED, and MaxQB for WNK4 Gene



SOURCE GeneReport for Unigene cluster for WNK4 Gene Hs.105448

mRNA Expression by UniProt/SwissProt for WNK4 Gene

Q96J92-WNK4_HUMAN
Tissue specificity: Expressed in kidney, colon and skin.
genes like me logo Genes that share expression patterns with WNK4: view

Protein tissue co-expression partners for WNK4 Gene

Primer Products

In Situ Assay Products

Orthologs for WNK4 Gene

This gene was present in the common ancestor of eukaryotes.

Orthologs for WNK4 Gene

Organism Taxonomy Gene Similarity Type Details
chimpanzee
(Pan troglodytes)
Mammalia WNK4 36
  • 99 (a)
OneToOne
WNK4 35
  • 99.44 (n)
  • 99.36 (a)
cow
(Bos Taurus)
Mammalia WNK4 36
  • 89 (a)
OneToOne
WNK4 35
  • 88.78 (n)
  • 88.73 (a)
dog
(Canis familiaris)
Mammalia WNK4 35
  • 87.23 (n)
  • 87.31 (a)
WNK4 36
  • 60 (a)
OneToOne
mouse
(Mus musculus)
Mammalia Wnk4 16
Wnk4 35
  • 85.31 (n)
  • 87.55 (a)
Wnk4 36
  • 88 (a)
OneToOne
oppossum
(Monodelphis domestica)
Mammalia WNK4 36
  • 76 (a)
OneToOne
platypus
(Ornithorhynchus anatinus)
Mammalia WNK4 36
  • 56 (a)
OneToOne
rat
(Rattus norvegicus)
Mammalia Wnk4 35
  • 84.96 (n)
  • 87.14 (a)
chicken
(Gallus gallus)
Aves LOC777580 35
  • 70.94 (n)
  • 71.79 (a)
WNK4 36
  • 49 (a)
OneToOne
lizard
(Anolis carolinensis)
Reptilia WNK4 36
  • 48 (a)
OneToOne
zebrafish
(Danio rerio)
Actinopterygii CABZ01069042.1 36
  • 31 (a)
OneToMany
CABZ01084815.1 36
  • 31 (a)
OneToMany
WNK4 (1 of 4) 36
  • 87 (a)
OneToMany
WNK4 (3 of 4) 36
  • 37 (a)
OneToMany
fruit fly
(Drosophila melanogaster)
Insecta Wnk 36
  • 14 (a)
OneToMany
worm
(Caenorhabditis elegans)
Secernentea wnk-1 36
  • 19 (a)
OneToMany
rice
(Oryza sativa)
Liliopsida Os11g0160300 35
  • 51.62 (n)
  • 48.51 (a)
wheat
(Triticum aestivum)
Liliopsida Ta.28467 35
sea squirt
(Ciona savignyi)
Ascidiacea -- 36
  • 72 (a)
OneToMany
Species with no ortholog for WNK4:
  • A. gosspyii yeast (Ashbya gossypii)
  • Actinobacteria (Mycobacterium tuberculosis)
  • African clawed frog (Xenopus laevis)
  • African malaria mosquito (Anopheles gambiae)
  • Alicante grape (Vitis vinifera)
  • alpha proteobacteria (Wolbachia pipientis)
  • amoeba (Dictyostelium discoideum)
  • Archea (Pyrococcus horikoshii)
  • baker's yeast (Saccharomyces cerevisiae)
  • barley (Hordeum vulgare)
  • beta proteobacteria (Neisseria meningitidis)
  • bread mold (Neurospora crassa)
  • Chromalveolata (Phytophthora infestans)
  • common water flea (Daphnia pulex)
  • corn (Zea mays)
  • E. coli (Escherichia coli)
  • filamentous fungi (Aspergillus nidulans)
  • Firmicute bacteria (Streptococcus pneumoniae)
  • fission yeast (Schizosaccharomyces pombe)
  • green algae (Chlamydomonas reinhardtii)
  • honey bee (Apis mellifera)
  • K. lactis yeast (Kluyveromyces lactis)
  • loblloly pine (Pinus taeda)
  • malaria parasite (Plasmodium falciparum)
  • medicago trunc (Medicago Truncatula)
  • moss (Physcomitrella patens)
  • orangutan (Pongo pygmaeus)
  • pig (Sus scrofa)
  • rainbow trout (Oncorhynchus mykiss)
  • rice blast fungus (Magnaporthe grisea)
  • schistosome parasite (Schistosoma mansoni)
  • sea anemone (Nematostella vectensis)
  • sea urchin (Strongylocentrotus purpuratus)
  • sorghum (Sorghum bicolor)
  • soybean (Glycine max)
  • stem rust fungus (Puccinia graminis)
  • sugarcane (Saccharum officinarum)
  • thale cress (Arabidopsis thaliana)
  • tomato (Lycopersicon esculentum)
  • toxoplasmosis (Toxoplasma gondii)
  • Trichoplax (Trichoplax adhaerens)
  • tropical clawed frog (Silurana tropicalis)

Evolution for WNK4 Gene

ENSEMBL:
Gene Tree for WNK4 (if available)
TreeFam:
Gene Tree for WNK4 (if available)

Paralogs for WNK4 Gene

Paralogs for WNK4 Gene

genes like me logo Genes that share paralogs with WNK4: view

Variants for WNK4 Gene

Sequence variations from dbSNP and Humsavar for WNK4 Gene

SNP ID Clin Chr 17 pos Sequence Context AA Info Type
VAR_017588 Pseudohypoaldosteronism 2B (PHA2B)
VAR_017589 Pseudohypoaldosteronism 2B (PHA2B)
VAR_017590 Pseudohypoaldosteronism 2B (PHA2B)
VAR_017591 Pseudohypoaldosteronism 2B (PHA2B)
VAR_041330 An ovarian mucinous carcinoma sample

Structural Variations from Database of Genomic Variants (DGV) for WNK4 Gene

Variant ID Type Subtype PubMed ID
esv33998 OTHER Inversion 15654335
nsv833450 CNV Loss 17160897
nsv908257 CNV Loss 21882294
nsv827998 CNV Loss 20364138

Variation tolerance for WNK4 Gene

Residual Variation Intolerance Score: 76.7% of all genes are more intolerant (likely to be disease-causing)
Gene Damage Index Score: 8.06; 84.37% of all genes are more intolerant (likely to be disease-causing)

Relevant External Links for WNK4 Gene

HapMap Linkage Disequilibrium report
WNK4
Human Gene Mutation Database (HGMD)
WNK4

No data available for Polymorphic Variants from UniProtKB/Swiss-Prot for WNK4 Gene

Disorders for WNK4 Gene

MalaCards: The human disease database

(10) MalaCards diseases for WNK4 Gene - From: OMIM, ClinVar, GeneTests, Orphanet, Swiss-Prot, DISEASES, Novoseek, and GeneCards

Disorder Aliases PubMed IDs
pseudohypoaldosteronism, type iib
  • pseudohypoaldosteronism type iib
pseudohypoaldosteronism
bartter disease
  • aldosteronism with hyperplasia of the adrenal cortex
arthrogryposis, distal, type 3
  • gordon syndrome
renal tubular transport disease
  • inborn renal tubular transport disorder
- elite association - COSMIC cancer census association via MalaCards
Search WNK4 in MalaCards View complete list of genes associated with diseases

UniProtKB/Swiss-Prot

WNK4_HUMAN
  • Pseudohypoaldosteronism 2B (PHA2B) [MIM:614491]: An autosomal dominant disorder characterized by hypertension, hyperkalemia, hyperchloremia, mild hyperchloremic metabolic acidosis, and correction of physiologic abnormalities by thiazide diuretics. {ECO:0000269 PubMed:11498583}. Note=The disease is caused by mutations affecting the gene represented in this entry.

Relevant External Links for WNK4

Genetic Association Database (GAD)
WNK4
Human Genome Epidemiology (HuGE) Navigator
WNK4
Atlas of Genetics and Cytogenetics in Oncology and Haematology:
WNK4
genes like me logo Genes that share disorders with WNK4: view

No data available for Genatlas for WNK4 Gene

Publications for WNK4 Gene

  1. Association of Ala589Ser polymorphism of WNK4 gene with essential hypertension in a high-risk Chinese population. (PMID: 19340547) Sun Z.J. … Zhao Y.Y. (J Physiol Sci 2009) 3 23 48 67
  2. WNK4 enhances the degradation of NCC through a sortilin-mediated lysosomal pathway. (PMID: 19875813) Zhou B. … Cai H. (J. Am. Soc. Nephrol. 2010) 3 23
  3. WNK4 diverts the thiazide-sensitive NaCl cotransporter to the lysosome and stimulates AP-3 interaction. (PMID: 19401467) Subramanya A.R. … Welling P.A. (J. Biol. Chem. 2009) 3 23
  4. Src family protein tyrosine kinase (PTK) modulates the effect of SGK1 and WNK4 on ROMK channels. (PMID: 19706464) Yue P. … Wang W.H. (Proc. Natl. Acad. Sci. U.S.A. 2009) 3 23
  5. A patient with pseudohypoaldosteronism type II caused by a novel mutation in WNK4 gene. (PMID: 19016006) Gong H. … Ning G. (Endocrine 2008) 3 23

Products for WNK4 Gene

Sources for WNK4 Gene

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